Water → 4-[(9R)-4-Chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyric acid

Temperature

80 °C

Ethyl 4-[(9R)-4-chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyrate (92.2 g) was dissolved in ethanol (100 ml), 4N aqueous sodium hydroxide (100 ml) was added, and the mixture was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature, water (200 ml) was added, and the mixture was washed twice with toluene (100 ml). The obtained aqueous layer was neutralized with concentrated hydrochloric acid (40 ml), and extracted twice with ethyl acetate (300 ml). The obtained ethyl acetate extract was washed successively with water (100 ml, twice), and saturated brine (100 ml), anhydrous magnesium sulfate and activated carbon (4.2 g) were added, and the mixture was stirred at room temperature for 10 min. The insoluble material was filtered off, and the solvent in the filtrate was evaporated. To the obtained residue was added chloroform (80 ml), and the mixture was heated to 50° C. Hexane (400 ml) was added dropwise, and the mixture was stirred at the same temperature for 30 min, and at room temperature for 2 hr. The precipitated solid was collected by filtration, washed with a mixed solvent of hexane and chloroform (hexane:chloroform=9:1, 50 ml), and dried under reduced pressure at 80° C. for 2 hr to give the title compound (72.5 g).

1. temperatureThe reaction mixture was cooled to room temperature
2. washthe mixture was washed twice with toluene (100 ml)
3. extractionextracted twice with ethyl acetate (300 ml)
4. extractionThe obtained ethyl acetate extract
5. washwas washed successively with water (100 ml
6. additiontwice), and saturated brine (100 ml), anhydrous magnesium sulfate and activated carbon (4.2 g) were added
7. stirringthe mixture was stirred at room temperature for 10 min
8. filtrationThe insoluble material was filtered off
9. customthe solvent in the filtrate was evaporated
10. additionTo the obtained residue was added chloroform (80 ml)
11. temperaturethe mixture was heated to 50° C
12. additionHexane (400 ml) was added dropwise
13. stirringthe mixture was stirred at the same temperature for 30 min
14. waitat room temperature for 2 hr
15. filtrationThe precipitated solid was collected by filtration
16. washwashed with a mixed solvent of hexane and chloroform (hexane:chloroform=9:1, 50 ml)
17. customdried under reduced pressure at 80° C. for 2 hr

ORD record

ord-2624360ae117463a803cd2df9fc1ac05

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040717B2